The syndecans are a family of cell surface heparan sulfate proteoglycans that participate in regulating cell behaviors including cell proliferation, cell migration and adhesion. Past studies suggest that these activities are largely dependent on syndecan heparan sulfate chains, while the role of the individual syndecan core proteins remains poorly understood. However, evidence is emerging that these proteins have specialized binding and signaling functions. The proposed work will examine the various binding interactions and signaling functions of the syndecan core protein domains. Studies will (i) employ a facile adhesion and spreading assay to document syndecan signaling and identify signaling domains in the core protein, (ii) use in vitro and in vivo assays to identify binding partners of the syndecan cytoplasmic domain and (iii) identify and characterize a receptor that binds to the extracellular protein domain of syndecan-4. Results will lead to a better understanding of epithelial morphogenesis and to the mechanisms that regulate tumor cell metastasis and invasion.